4.5 Article

Aging reduces succinate dehydrogenase activity in rat type IIx/IIb diaphragm muscle fibers

Journal

JOURNAL OF APPLIED PHYSIOLOGY
Volume 128, Issue 1, Pages 70-77

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.00644.2019

Keywords

aging; diaphragm; fiber type; oxygen consumption; sarcopenia; succinate dehydrogenase

Funding

  1. National Institutes of Health [AG057052, AG-044615]

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In aged rats, diaphragm muscle (DIAm) reduced specific force and fiber cross-sectional area, sarcopenia, is selective for vulnerable type IIx and/or IIb DIAm fibers, with type I and IIa fibers being resilient. In humans, the oxidative capacity [as measured by maximum succinate dehydrogenase (SDHmax) activity] of fast-type muscle is reduced with aging. with slow-type muscle being unaffected. We hypothesized that in aged Fischer rat DIAm exhibiting sarcopenia, reduced SDHmax activity would occur in type Mx and/or IIb fibers. Rats obtained from the NIA colony (6, 18, and 24 mo old) were euthanized, and similar to 2-mm-wide DIAm strips were obtained. For SDHmax and fiber type assessments, DIAm strips were stretched (approximately optimal length), fresh frozen in isopentane, and sectioned on a cryostat at 6 mu m. SDHmax quantified by intensity of nitroblue tetrazolium diformazan precipitation. was assessed in a fiber type-specific manner by comparing serial sections labeled with myosin heavy chain (MyHC) antibodies differentiating type I (MyHC(slow)), IIa (MyHC(2A)), and IIx and/or IIb fibers. Isometric DIAm force and fatigue were assessed in DIAm strips by muscle stimulation with supramaximal pulses at a variety of frequencies (5-1(X) Hz) delivered in 1-s trains. By 24 mo, DIAm sarcopenia was apparent and SDHmax in type IIx and/or IIb fibers activity was reduced similar to 35% compared with 6-mo-old control DIAm. These results underscore the remarkable fiber type selectivity of type IIx and/or IIb fibers to age-associated perturbations and suggest that reduced mitochondrial oxidative capacity is associated with DIAm sarcopenia. NEW & NOTEWORTHY We examined the oxidative capacity as measured by maximum succinate dehydrogenase activity in older (18 or 24 mo old) Fischer 344 rat diaphragm muscle (DIAm) compared with young rats (6 mo old). In 24-mo-old rats, SDH activity was reduced in type IIx/b DIAm fibers. These SDH changes were concomitant with sarcopenia (reduced specific force and atrophy of type Ibc/b DIAm fibers) at 24 mo old. At 18 mo old, there was no change in SDH activity and no evidence of sarcopenia.

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